O43164 (PJA2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
E3 ubiquitin-protein ligase Praja-2
Short name=Praja2
EC=6.3.2.-

Alternative name(s):
RING finger protein 131

Gene names

Name:	PJA2
Synonyms:	KIAA0438, RNF131

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	708 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Has E2-dependent E3 ubiquitin-protein ligase activity. Responsible for ubiquitination of cAMP-dependent protein kinase type I and type II-alpha/beta regulatory subunits and for targeting them for proteasomal degradation. Essential for PKA-mediated long-term memory processes. Ref.9 Ref.14
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Binds ubiquitin-conjugating enzymes (E2s). In vitro, interacts with the ubiquitin-conjugating enzyme, UBE2D2. The phosphorylated form interacts with PRKAR1A, PRKAR2A and PRKAR2B. Binds the catalytic subunits of cAMP-dependent protein kinase. Ref.9 Ref.14
Subcellular location	Cytoplasm. Cell membrane. Endoplasmic reticulum membrane; Peripheral membrane protein. Golgi apparatus membrane; Peripheral membrane protein. Cell junction › synapse By similarity. Cell junction › synapse › postsynaptic cell membrane › postsynaptic density By similarity. Note: Localizes at the cytoplasmic side of endoplasmic reticulum and Golgi apparatus. Expressed in the postsynaptic density region of synapses By similarity. Co-localizes with PRKAR2A and PRKAR2B in the cytoplasm and the cell membrane. Ref.14
Sequence similarities	Contains 1 RING-type zinc finger.
Sequence caution	The sequence BAA23710.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cell junction Cell membrane Cytoplasm Endoplasmic reticulum Golgi apparatus Membrane Postsynaptic cell membrane Synapse
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	long-term memory Inferred from sequence or structural similarity. Source: UniProtKB regulation of protein kinase A signaling cascade Inferred from mutant phenotype Ref.14. Source: UniProtKB
Cellular_component	Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell cell junction Inferred from electronic annotation. Source: UniProtKB-KW cytoplasm Inferred from direct assay Ref.14. Source: UniProtKB endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from direct assay Ref.14. Source: UniProtKB postsynaptic density Inferred from electronic annotation. Source: UniProtKB-SubCell postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	protein kinase A catalytic subunit binding Inferred from mutant phenotype Ref.14. Source: UniProtKB protein kinase A regulatory subunit binding Inferred from mutant phenotype Ref.14. Source: UniProtKB ubiquitin-protein ligase activity Inferred from direct assay Ref.14. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O43164-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O43164-2)

The sequence of this isoform differs from the canonical sequence as follows:
     544-563: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.7
	Chain	2 – 708	707	E3 ubiquitin-protein ligase Praja-2		PRO_0000278230
Regions
	Zinc finger	634 – 675	42	RING-type; atypical
	Region	531 – 708	178	Interaction with PRKAR1A, PRKAR2A and PRKAR2B
Amino acid modifications
	Modified residue	2	1	N-acetylserine Ref.7
	Modified residue	309	1	Phosphoserine Ref.15
	Modified residue	323	1	Phosphoserine Ref.12
	Modified residue	342	1	Phosphoserine; by PKA Ref.14
	Modified residue	389	1	Phosphothreonine; by PKA Ref.14
	Modified residue	432	1	Phosphoserine Ref.10
Natural variations
	Alternative sequence	544 – 563	20	Missing in isoform 2.		VSP_023198
	Natural variant	176	1	E → G. Corresponds to variant rs35224970 [ dbSNP | Ensembl ].		VAR_057215
	Natural variant	297	1	Q → R. Ref.1 Ref.6 Corresponds to variant rs1045706 [ dbSNP | Ensembl ].		VAR_030698
	Natural variant	705	1	A → T. Corresponds to variant rs246105 [ dbSNP | Ensembl ].		VAR_030699

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 24, 2009. Version 4. Checksum: 719B4A367C411735	FASTA	708	78,214
	10 20 30 40 50 60 MSQYTEKEPA AMDQESGKAV WPKPAGGYQT ITGRRYGRRH AYVSFKPCMT RHERSLGRAG 70 80 90 100 110 120 DDYEVLELDD VPKENSSGSS PLDQVDSSLP SEPIFEKSET EIPTCGSALN QTTESSQSFV 130 140 150 160 170 180 AVHHSEEGRD TLGSSTNLHN HSEGEYIPGA CSASSVQNGI ALVHTDSYDP DGKHGEDNDH 190 200 210 220 230 240 LQLSAEVVEG SRYQESLGNT VFELENREAE AYTGLSPPVP SFNCEVRDEF EELDSVPLVK 250 260 270 280 290 300 SSAGDTEFVH QNSQEIQRSS QDEMVSTKQQ NNTSQERQTE HSPEDAACGP GHICSEQNTN 310 320 330 340 350 360 DREKNHGSSP EQVVRPKVRK LISSSQVDQE TGFNRHEAKQ RSVQRWREAL EVEESGSDDL 370 380 390 400 410 420 LIKCEEYDGE HDCMFLDPPY SRVITQRETE NNQMTSESGA TAGRQEVDNT FWNGCGDYYQ 430 440 450 460 470 480 LYDKDEDSSE CSDGEWSASL PHRFSGTEKD QSSSDESWET LPGKDENEPE LQSDSSGPEE 490 500 510 520 530 540 ENQELSLQEG EQTSLEEGEI PWLQYNEVNE SSSDEGNEPA NEFAQPAFML DGNNNLEDDS 550 560 570 580 590 600 SVSEDLDVDW SLFDGFADGL GVAEAISYVD PQFLTYMALE ERLAQAMETA LAHLESLAVD 610 620 630 640 650 660 VEVANPPASK ESIDGLPETL VLEDHTAIGQ EQCCPICCSE YIKDDIATEL PCHHFFHKPC 670 680 690 700 VSIWLQKSGT CPVCRRHFPP AVIEASAAPS SEPDPDAPPS NDSIAEAP
	Isoform 2 [UniParc]. Checksum: 34A652ACAF3A02FE	FASTA	688	76,091
	10 20 30 40 50 60 MSQYTEKEPA AMDQESGKAV WPKPAGGYQT ITGRRYGRRH AYVSFKPCMT RHERSLGRAG 70 80 90 100 110 120 DDYEVLELDD VPKENSSGSS PLDQVDSSLP SEPIFEKSET EIPTCGSALN QTTESSQSFV 130 140 150 160 170 180 AVHHSEEGRD TLGSSTNLHN HSEGEYIPGA CSASSVQNGI ALVHTDSYDP DGKHGEDNDH 190 200 210 220 230 240 LQLSAEVVEG SRYQESLGNT VFELENREAE AYTGLSPPVP SFNCEVRDEF EELDSVPLVK 250 260 270 280 290 300 SSAGDTEFVH QNSQEIQRSS QDEMVSTKQQ NNTSQERQTE HSPEDAACGP GHICSEQNTN 310 320 330 340 350 360 DREKNHGSSP EQVVRPKVRK LISSSQVDQE TGFNRHEAKQ RSVQRWREAL EVEESGSDDL 370 380 390 400 410 420 LIKCEEYDGE HDCMFLDPPY SRVITQRETE NNQMTSESGA TAGRQEVDNT FWNGCGDYYQ 430 440 450 460 470 480 LYDKDEDSSE CSDGEWSASL PHRFSGTEKD QSSSDESWET LPGKDENEPE LQSDSSGPEE 490 500 510 520 530 540 ENQELSLQEG EQTSLEEGEI PWLQYNEVNE SSSDEGNEPA NEFAQPAFML DGNNNLEDDS 550 560 570 580 590 600 SVSEAISYVD PQFLTYMALE ERLAQAMETA LAHLESLAVD VEVANPPASK ESIDGLPETL 610 620 630 640 650 660 VLEDHTAIGQ EQCCPICCSE YIKDDIATEL PCHHFFHKPC VSIWLQKSGT CPVCRRHFPP 670 680 AVIEASAAPS SEPDPDAPPS NDSIAEAP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro." Ishikawa K., Nagase T., Nakajima D., Seki N., Ohira M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 4:307-313(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ARG-297. Tissue: Brain.
[2]	"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones." Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T. Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Placenta.
[4]	"The DNA sequence and comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M. Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ARG-297. Tissue: Brain.
[7]	Bienvenut W.V., Waridel P., Quadroni M. Submitted (MAR-2009) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-18; 24-34; 59-73; 193-207; 241-258; 388-404 AND 583-610, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[8]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 456-708 (ISOFORM 2). Tissue: Liver.
[9]	"PJA1, encoding a RING-H2 finger ubiquitin ligase, is a novel human X chromosome gene abundantly expressed in brain." Yu P., Chen Y., Tagle D.A., Cai T. Genomics 79:869-874(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH UBE2D2.
[10]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-432, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[12]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-323, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[13]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[14]	"Control of PKA stability and signalling by the RING ligase praja2." Lignitto L., Carlucci A., Sepe M., Stefan E., Cuomo O., Nistico R., Scorziello A., Savoia C., Garbi C., Annunziato L., Feliciello A. Nat. Cell Biol. 13:412-422(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PRKAR1A; PRKAR2A AND PRKAR2B, PHOSPHORYLATION AT SER-342 AND THR-389.
[15]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-309, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB007898 mRNA. Translation: BAA23710.2. Different initiation. AK291759 mRNA. Translation: BAF84448.1. AC008467 Genomic DNA. No translation available. AC010625 Genomic DNA. No translation available. CH471086 Genomic DNA. Translation: EAW49050.1. CH471086 Genomic DNA. Translation: EAW49051.1. BC030826 mRNA. Translation: AAH30826.1. CR749579 mRNA. Translation: CAH18371.1.
IPI	IPI00006557. IPI00827761.
PIR	T00064.
RefSeq	NP_055634.3. NM_014819.4.
UniGene	Hs.483036. Hs.592564.
3D structure databases
ProteinModelPortal	O43164.
SMR	O43164. Positions 603-680.
ModBase	Search...
Protein-protein interaction databases
IntAct	O43164. 15 interactions.
STRING	9606.ENSP00000354775.
PTM databases
PhosphoSite	O43164.
Proteomic databases
PaxDb	O43164.
PRIDE	O43164.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000361189; ENSP00000354775; ENSG00000198961. ENST00000361557; ENSP00000355284; ENSG00000198961.
GeneID	9867.
KEGG	hsa:9867.
UCSC	uc003kos.4. human.
Organism-specific databases
CTD	9867.
GeneCards	GC05M108698.
H-InvDB	HIX0005075.
HGNC	HGNC:17481. PJA2.
HPA	HPA040347.
neXtProt	NX_O43164.
PharmGKB	PA134873520.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG272750.
HOGENOM	HOG000230900.
HOVERGEN	HBG003815.
InParanoid	O43164.
KO	K10634.
OMA	PEAFMLD.
OrthoDB	EOG4D52XB.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
UniPathway	UPA00143.
Gene expression databases
Bgee	O43164.
CleanEx	HS_PJA2.
Genevestigator	O43164.
Family and domain databases
Gene3D	3.30.40.10. 1 hit.
InterPro	IPR001841. Znf_RING. IPR013083. Znf_RING/FYVE/PHD. [Graphical view]
Pfam	PF13639. zf-RING_2. 1 hit. [Graphical view]
SMART	SM00184. RING. 1 hit. [Graphical view]
PROSITE	PS00518. ZF_RING_1. False negative. PS50089. ZF_RING_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	PJA2. human.
GenomeRNAi	9867.
NextBio	37195.

Entry information

Entry name

PJA2_HUMAN

Accession

Primary (citable) accession number: O43164
Secondary accession number(s): A8K6U4 , D3DSZ5, Q68D49, Q8N1G5

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 20, 2007
Last sequence update:	November 24, 2009
Last modified:	May 29, 2013
This is version 106 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.